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Mosaic loss of Y chromosome (mLOY) in blood cells is an age-related somatic mosaicism event, but its relationship with pulmonary health remains undercharacterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To examine the association between mLOY and pulmonary outcomes in men.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Leveraging mLOY assessment (cell fraction\u2009\u2265\u20095%) in over 12\u00a0000 men, including 5097 from the COPDGene Study and 7235 from six additional cohorts in the Trans-Omics for Precision Medicine program, we investigated mLOY associations with respiratory outcomes and epigenetic aging using multivariable cross-sectional, longitudinal, and prospective models. Primary outcomes included spirometry, CT-based emphysema, and epigenetic pace of aging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The prevalence of mLOY increased with age. Cross-sectionally, mLOY was associated with airflow obstruction, with reduced FEV1\/FVC of 0.018 [95% CI, \u22120.030 to \u22120.006] in COPDGene and 0.020 [95% CI, \u22120.027 to \u22120.013] in TOPMed. mLOY was also associated with greater CT-quantified lung emphysema and faster pace epigenetic aging. Longitudinally, mLOY was associated with faster FEV1 decline (\u223c55mL\/year vs \u223c38mL\/year). Prospectively, mLOY was associated with higher odds of developing COPD [OR\u2009=\u20091.84, 95% CI, 1.10-3.07] and preserved ratio impaired spirometry (PRISm) [OR\u2009=\u20092.87, 95% CI, 1.09-7.56] among participants with normal lung function at baseline. Associations remained robust after adjusting for clonal hematopoiesis and telomere length.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>mLOY is associated with lower lung function, accelerated lung function decline, higher emphysema, and faster pace of aging, positioning mLOY as a potential biomarker of respiratory aging in men.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajrccm\/aamag120","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T04:32:35Z","timestamp":1773981155000},"page":"1483-1494","source":"Crossref","is-referenced-by-count":2,"title":["Mosaic loss of Y chromosome associates with lung function, emphysema, and epigenetic aging"],"prefix":"10.1093","volume":"212","author":[{"given":"Woei-Yuh","family":"Saw","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and 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